Daniel H Wreschner
Professor, Tel Aviv University, Israel
Dr. Wreschner, is a world recognized leader in cancer research and has published extensively in highly-regarded scientific journals in the areas of tumor proteins and their role in tumor cell growth.
Dr. Wreschner carried out research at the two premier research institutions in London, the National Institute of Medical Research, and the Imperial Cancer Research Fund (ICRF), investigating molecular mechanisms of interferon. The results emanating from these studies were published in leading journals, included two Nature publications - four of these articles have been since cited more than 200 times. Dr. Wreschner was the first to clone the very important cancer-associated gene MUC1. Several important ‘firsts’ in MUC1 biology are attributed to Dr. Wreschner, including the cloning of the MUC1 cDNAs and gene, the phosphorylation of the MUC1 protein and its participation in key cell-signalling pathways, the existence of alternative MUC1 splice forms and the self-cleavage of the MUC1 protein.
We are interested in discovering genes that code for novel secreted proteins that regulate cell differentiation and growth. C4orf48 is one of the several genes located in the critical locus of the Wolf–Hirschhorn syndrome (WHS) that manifests itself in physical and mental developmental abnormalities resulting from allelic loss of one or more genes present at this locus. It encodes a small protein of unknown function that is highly conserved amongst vertebrates and contains a typical secretory signal peptide. C4orf48 expression analyses revealed high expression in brain and testes and pronounced expression in pancreas and colon. Brain in-situ hybridization analyses demonstrated that C4orf48 is expressed in regions retaining neurogenic potential - The hippocampus, olfactory bulb and cerebellar cortex. Temporal analyses demonstrated much higher C4orf48 levels in brains from early post-natal (3-5 days post-partum) mice as compared to adults, whereas a temporally inverse pattern of expression is observed in testis - post-natal levels are low, and then peak in adults. Immunofluorescent analyses demonstrated high C4orf48 protein levels in post-natal pancreatic tissue as compared to lower levels in adult pancreatic tissue where C4orf48 protein located to peripheral cells of pancreatic islets. RNA-Seq analyses showed striking upregulation of C4orf48 expression in replicating cells isolated from islets. Prominent C4orf48 interacting proteins included TenascinC (TNC), Nell2 [Nell= Neural Epidermal growth factor (EGF)-Like] and RPTPβ (a receptor with tyrosine phosphatase activity) and BioGRID (Biological General Repository Interaction Dataset) reports C4orf48 interactions with TGFB1, NELL1 and NELL2. NELL1, NELL2 and TNC contain EGF module repeats, and all interacting proteins are secreted or membrane bound, expressed in the CNS and regulate developmental and differentiation processes. Taken together our findings suggest that C4orf48 is a novel secreted protein that plays a role in the differentiation of replicating cells present in various tissues.